Enhanced detection of myeloperoxidase activity in deep tissues through luminescent excitation of near-infrared nanoparticles.

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  • Author(s): Zhang N;Zhang N; Francis KP; Prakash A; Ansaldi D
  • Source:
    Nature medicine [Nat Med] 2013 Apr; Vol. 19 (4), pp. 500-5. Date of Electronic Publication: 2013 Mar 03.
  • Publication Type:
    Journal Article
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Nature Publishing Company Country of Publication: United States NLM ID: 9502015 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1546-170X (Electronic) Linking ISSN: 10788956 NLM ISO Abbreviation: Nat Med Subsets: MEDLINE
    • Publication Information:
      Publication: New York Ny : Nature Publishing Company
      Original Publication: New York, NY : Nature Pub. Co., [1995-
    • Subject Terms:
      Nanoparticles*; Luminescent Measurements/*methods ; Peroxidase/*metabolism; Animals ; Female ; Luminol ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, Nude ; Neoplasm Metastasis ; Neoplasms, Experimental/metabolism ; Pneumonia/metabolism ; Spectroscopy, Near-Infrared
    • Abstract:
      A previous study reported the use of luminol for the detection of myeloperoxidase (MPO) activity using optical imaging in infiltrating neutrophils under inflammatory disease conditions. The detection is based on a photon-emitting reaction between luminol and an MPO metabolite. Because of tissue absorption and scattering, however, luminol-emitted blue light can be efficiently detected from superficial inflammatory foci only. In this study we report a chemiluminescence resonance energy transfer (CRET) methodology in which luminol-generated blue light excites nanoparticles to emit light in the near-infrared spectral range, resulting in remarkable improvement of MPO detectability in vivo. CRET caused a 37-fold increase in luminescence emission over luminol alone in detecting MPO activity in lung tissues after lipopolysaccharide challenge. We demonstrated a dependence of the chemiluminescent signal on MPO activity using MPO-deficient mice. In addition, co-administration of 4-aminobenzoic acid hydrazide (4-ABAH), an irreversible inhibitor of MPO, significantly attenuated luminescent emission from inflamed lungs. Inhibition of nitric oxide synthase with a nonspecific inhibitor, L-NAME, had no effect on luminol-mediated chemiluminescence production. Pretreatment of mice with MLN120B, a selective inhibitor of IKK-2, resulted in suppression of neutrophil infiltration to the lung tissues and reduction of MPO activity. We also demonstrated that CRET can effectively detect MPO activity at deep tissue tumor foci due to tumor development-associated neutrophil infiltration. We developed a sensitive MPO detection methodology that provides a means for visualizing and quantifying oxidative stress in deep tissue. This method is amenable to rapid evaluation of anti-inflammatory agents in animal models.
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    • Accession Number:
      5EXP385Q4F (Luminol)
      EC 1.11.1.7 (Peroxidase)
    • Publication Date:
      Date Created: 20130305 Date Completed: 20130604 Latest Revision: 20211021
    • Publication Date:
      20221213
    • Accession Number:
      10.1038/nm.3110
    • Accession Number:
      23455711